Complete Androgen Insensitivity Syndrome and bone mass. Basal evaluation and after long term estrogen treatment

L’osso è un tessuto target per estrogeni ed androgeni ma l’azione singola e la sinergia tra i due non sono compresi interamente. Le donne affette da Sindrome da Insensititvità Completa agli Androgeni (CAIS) hanno un cariotipo 46XY ma presentano una completa inattività del recettore degli androgeni. Nello studio abbiamo valutato la densità minerale ossea (BMD) in un gruppo di donne adulte CAIS sottoposte a gonadectomia al momento della prima visita e dopo almeno 12 mesi di terapia estrogenica. Il principale obiettivo è stato di valutare se, nelle donne CAIS, una ottimale estrogenizzazione fosse sufficiente a mantenere/ripristinare una adeguata BMD. 24 donne CAIS sono state sottoposte a DXA lombare e femorale all'arruolamento nello studio (t1), dopo terapia estrogenica di 12mesi(t2) e oltre (t>2). Sono state valutate: BMD(g/cm2) e Zscore lombare e femorale (a t1,t2 e t>2) E’ stato considerato se fossero rilevanti l’essere (gruppo1) o meno (gruppo 2) in terapia ormonale al t1 e l’età della gonadectomia. Risultati: Al t1 BMD e Zscore lombari e femorale erano significativamente ridotti rispetto alla popolazione controllo nel campione totale (lombare 0,900+0,12; -1,976+0,07, femorale 0,831 + 0,14; -1,385+0,98), nel gruppo 1 (lombare 0,918+0,116;-1,924+0,79, femorale 0,824+0,13;-1,40+1,00) e nel gruppo 2 (lombare 0.845+0,11 -2,13+1,15, femorale 0,857+0,17;-1,348+1,05) Al t2 e t>2 la BMD lombare è risultata significativamente aumentata (p=0,05 e p=0,02). Zscore lombare, BMD e Zscore femorale non hanno dimostrato variazioni significative. L’aver effettuato la gonadectomia in età post puberale è associato a Zscore lombare e femorale più elevati al t1. Nelle donne CAIS la terapia estrogenica è indispensabile per prevenire un'ulteriore perdita di BMD ma, da sola, non sembra in grado di ripristinare normali valori di BMD.I risultati del nostro studio supportano la tesi che gli androgeni, mediante l’azione recettoriale, abbiano un' azione diretta nel raggiungere e mantenere la BMD.Bone is a target tissue for both estrogens and androgens. Women with Complete Androgen Insensitivity Syndrome (CAIS)present with a 46XY cariotype but absence of receptorial androgen action. In our study we evaluated bone mineral density (BMD)among adult CAIS women who previously underwent bilateral gonadectomy at recruitment and after at least 12 month estrogen treatment. The main goal was to evaluate if full dosage estrogen only therapy was enough to preserve/improve BMD. 24 CAIS women underwent lumbar spine and hip DXA scan at recruitment (t1), after estrogen treatment of 12 months (t1) and more (t>2). BMD(g/cm2),lumbar spine (L2-L4) and hip Zscore at t1,t2 e t>2 were evaluated. It was considered wether (group1) or not (group2) women were on hormonal treatment at recruitment and age at gonadectomy. Results:at t1 BMD and Z score at spine and hip were significantly reduced when compared to control population in all groups: all population (spine 0,900+0,12; -1,976+0,07, hip 0,831 + 0,14; -1,385+0,98) , group 1 (spine 0,918+0,116;-1,924+0,79, hip 0,824+0,13;-1,40+1,00) and group 2 (spine 0.845+0,11-2,13+1,15, hip 0,857+0,17;-1,348+1,05).At t2 and t>2 spine BMD and Zscore were significantly increased (p=0,05 e p=0,02). Spine Zscore, hip BMD and Zscore did not show significant changes. Postpubertal age at gonadectomy was related to higher lumbar spine and hip Zscore at t1 In CAIS women estrogen therapy is essential to prevent further bone loss but it doesn't seem to restore normal BMD values. Our study support the hypothesis that androgen, thorough receptorial action, have a direct role in reaching and preserving BMD

Setting priorities in clinical and health services research: properties of an adapted and updated method

Objectives: the objectives of this study is to review the set of criteria of the Institute of Medicine (IOM) for priority-setting in research with addition of new criteria if necessary, and to develop and evaluate the reliability and validity of the final priority score. Methods: based on the evaluation of 199 research topics, forty-five experts identified additional criteria for priority-setting, rated their relevance, and ranked and weighted them in a three-round modified Delphi technique. A final priority score was developed and evaluated. Internal consistency, test-retest and inter-rater reliability were assessed. Correlation with experts' overall qualitative topic ratings were assessed as an approximation to validity. Results: all seven original IOM criteria were considered relevant and two new criteria were added ('potential for translation into practice', and 'need for knowledge'). Final ranks and relative weights differed from those of the original IOM criteria: 'research impact on health outcomes' was considered the most important criterion (4.23), as opposed to 'burden of disease' (3.92). Cronbach's alpha (0.75) and test-retest stability (interclass correlation coefficient = 0.66) for the final set of criteria were acceptable. The area under the receiver operating characteristic curve for overall assessment of priority was 0.66. Conclusions: a reliable instrument for prioritizing topics in clinical and health services research has been developed. Further evaluation of its validity and impact on selecting research topics is required

Assessment of the impact of a clinical and health services research call in Catalonia

This article presents the ex-post assessment of a program of clinical and health services research and the evaluation of the social impact. The Catalan Agency for Health Information, Assessment, and Quality (CAHIAQ) promotes a biannual open, public, competitive extramural research call to conduct non-commercial clinical and health services research. Its aim is to address local needs of research (knowledge gaps) and to assess the implementation of innovation. Approximately 5.8 million Euros have been allocated to the call. To meet the Agency’s mission, a periodical ‘call for expressions of interest’ and topic prioritization is organized prior to the research call. The awarded projects are submitted to an ex-ante, ongoing, and ex-post assessment. Impact assessment of the research call on advancing knowledge and healthcare decision making is based on the Canadian Academy of Health Sciences framework (Panel on Return on Investment in Health Research, 2009). The methods used include bibliometric analysis, surveys to researchers and decision-makers, and a more in-depth case study of translation pathways. This includes a crossover of cases from 1996 to 2004. Some results are compared against other international health services research calls. The conclusion is that local agencies can significantly contribute to fill knowledge gaps in a specific context. Assessment of the complete research cycle provides opportunities for improving the entire research process (identification of knowledge needs, call for proposals, funding allocation, research completion, subsequent impact). Specifically, assessment of the different types of impact of research development on knowledge generation and decision making closes the evaluation cycle fulfilling the Agency's mission.Fil: Adam, Paula. Catalan Agency for Health Information; España. Epidemiologia y Salud Pública; EspañaFil: Solans Doménech, Maite. Catalan Agency for Health Information; España. Epidemiologia y Salud Pública; EspañaFil: Pons, Joan M. V.. Catalan Agency for Health Information; España. Epidemiologia y Salud Pública; España. Gobierno de Catalunya. Ministerio de Salud; EspañaFil: Aymerich, Marta. Gobierno de Catalunia. Ministerio de Salud; España. Universidad de Girona; EspañaFil: Berra, Silvina del Valle. Universidad Nacional de Córdoba. Facultad de Medicina. Escuela de Salud Pública; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guillamon, Imma. Catalan Agency for Health Information; España. Epidemiologia y Salud Pública; EspañaFil: Sánchez, Emilia. Universitat Ramon Llull; EspañaFil: Permanyer Miralda, Gaieta. Catalan Agency for Health Information; España. Epidemiologia y Salud Pública; España. Universidad Autonoma de Barcelona. Hospital Vall D; Españ

El desafío familiar en el cuidado a las personas con transtorno mental

Objetivo: identificar os desafios encontrados pelos familiares que convivem com pessoas acometidas por transtorno mental. Método: pesquisa descritiva-exploratória, realizada em 2013. A coleta de dados se deu por meio de entrevista com 19 familiares de usuários de um CAPS II com diagnóstico de transtornos de esquizofrenia, transtorno afetivo bipolar e depressão em um município do Oeste de Santa Catarina/SC. A interpretação das informações ocorreu a partir da análise de conteúdo temática. O estudo teve o Parecer favorável do projeto pelo Comitê de Ética em Pesquisa, sob nº 159.215/2012. Resultados: na análise, emergiram quatro temas: Sobrecarga emocional dos familiares; Impacto que o transtorno mental causa nos cuidadores; Ações do familiar para o cuidado na crise; e Dificuldades dos familiares com manejo do transtorno. Conclusão: há necessidade da inclusão da família no tratamento e a importância de se olhar para a família.Objective: to identify the challenges found by families living with people suffering from mental disorder. Method: it is descriptive exploratory research, conducted in 2013. The data collection was carried out through interviews with 19 relatives of CAPS II patients with schizophrenia disorders, bipolar disorder and depression in a city in the West of Santa Catarina/SC. The interpretation of information occurred from the thematic content analysis. The study had a favorable opinion of the project by the Research Ethics Committee, under Number 159,215/2012. Results: from the analysis four themes emerged: The emotional burden of the family; Impact that mental illness causes in caregivers; Family´s actions for care during crisis; and Family difficulties to handle the disorder. Conclusion: it is necessary to include the family in the treatment and the importance of looking for the family.Objetivo: identificar los desafíos encontrados por los familiares que conviven con personas con trantorno mental. Método: investigación descriptiva exploratoria, realizada en 2013. La recolección de datos fue por medio de entrevista, con 19 familiares de usuarios de un CAPS II con diagnóstico de trastornos de esquizofrenia, trastorno afectivo bipolar y depresión en un municipio del Oeste de Santa Catarina/SC. La interpretación de las informaciones se dio a partir del análisis de contenido temático. El estudio tuvo el parecer favorable del proyecto por el Comité de Ética en Investigación, sobre nº 159.215/2012. Resultados: en el análisis surgieron cuatro temas: Sobrecarga emocional de los familiares; Impacto que el trastorno mental causa en los cuidadores; Acciones del familiar para el cuidado en la crisis; y, Dificultades de los familiares con manejo del trastorno. Conclusión: hay necesidad de la inclusión de la familia en el tratamiento y la importancia de observar a la familia

OnabotulinumtoxinA reduces temporal pain processing at spinal level in patients with lower limb spasticity

Spasticity is a muscle tone disorder associated with different neurological conditions. Spasticity could be associated with pain, high disability, poor functional recovery, and reduced quality of life. Botulinum neurotoxin type A (BoNT-A) is considered a first-line treatment for spasticity and, more recently, it also represents a therapeutic option for various chronic pain conditions. In this open label study, we aim to evaluate the effect of the BoNT-A on the spinal nociception in patients affected by spasticity of the lower limbs with associated pain with predominantly neuropathic features. Ten patients with stroke, 10 with multiple sclerosis and 5 with spinal cord injury were enrolled in the study. They were tested with clinical scales (neuropathic pain scale inventory (NPSI), numerical rating scale (NRS), modified Ashworth scale (MAS) and with the nociceptive withdrawal reflex at lower limbs to explore the spinal temporal summation threshold at baseline and 30 day after BoNT-A injection. OnabotulinumtoxinA (50 to 200 units per site) was injected in the lower limb muscles according to the distribution of spasticity. No significant differences were found at baseline for neurophysiological features across groups. After the BoNT-A injection, we recorded a significant reduction in MAS and NRS scores. Regarding the neurophysiological parameters, we described a significant increase in the temporal summation threshold after the BoNT-A injection. Our data supports the hypothesis that peripherally injected OnabotulinumtoxinA modulates the excitability of spinal cord nociceptive pathways. This activity may take place irrespective of the effect of the drug on spasticity

Standardised data collection for clinical follow-up and assessment of outcomes in differences of sex development (DSD): recommendations from the COST action DSDnet

The treatment and care of individuals who have a difference of sex development (DSD) have been revised over the past two decades and new guidelines have been published. In order to study the impact of treatments and new forms of management in these rare and heterogeneous conditions, standardised assessment procedures across centres are needed. Diagnostic work-up and detailed genital phenotyping are crucial at first assessment. DSDs may affect general health, have associated features or lead to comorbidities which may only be observed through lifelong follow-up. The impact of medical treatments and surgical (non-) interventions warrants special attention in the context of critical review of current and future care. It is equally important to explore gender development early and refer to specialised services if needed. DSDs and the medical, psychological, cultural and familial ways of dealing with it may affect self-perception, self-esteem, and psychosexual function. Therefore, psychosocial support has become one of the cornerstones in the multidisciplinary management of DSD, but its impact remains to be assessed. Careful clinical evaluation and pooled data reporting in a global DSD registry will allow linking genetic, metabolomic, phenotypic and psychological data. For this purpose, our group of clinical experts and patient and parent representatives designed a template for structured longitudinal follow-up. In this paper, we explain the rationale behind the selection of the dataset. This tool provides guidance to professionals caring for individuals with a DSD and their families. At the same time, it collects the data needed for answering unsolved questions of patients, clinicians, and researchers. Ultimately, outcomes for defined subgroups of rare DSD conditions should be studied through large collaborative endeavours using a common protocol

Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.Supported by grants from the Spanish Ministry of Science, Innovation and Universities (MCIU) co-financed with FEDER funds (SAF2015-65327-R and RTI2018-096494-B-100 to JA; BFU2016-76872-R to EB, AGL2017-86757-R to LA, SAF2017-87301-R to MLMC, SAF2015-64111-R to AP, SAF2015-73549-JIN to HR), Instituto de Salud Carlos III (PIE13/0004 to AP), the Basque Government Department of Health (2015111117 to LA), the Basque Foundation for Innovation and Health Research (BIOEF), through the EiTB Maratoia grant BIO15/CA/016/BS to MLMC, the regional Government of Andalusia co-funded by CEC and FEDER funds (Proyectos de Excelencia P12-CTS-2232) and Fundación Domingo Martínez (to AP). LA is supported by the Ramon y Cajal program (RYC-2013-13666). DB, MMR and TMM are recipients of MCIU FPI fellowships. ACG and AP are recipients of fellowships form the Basque Government. APC is a recipient of a fellowship from the University of the Basque Country. We thank the MCIU for the Severo Ochoa Excellence accreditation (SEV-2016-0644), the Basque Department of Industry, Tourism and Trade (Etortek and Elkartek programs), the Innovation Technology Department of the Bizkaia Province and the CIBERehd network. DB and JA are supported by a grant from the Jesús de Gangoiti Barrera Foundation

Fundulus as the premier teleost model in environmental biology : opportunities for new insights using genomics

Author Posting. © Elsevier B.V., 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology Part D: Genomics and Proteomics 2 (2007): 257-286, doi:10.1016/j.cbd.2007.09.001.A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an extensive body of work examining the adaptive responses of Fundulus species to environmental conditions, and describe how this research has contributed importantly to our understanding of physiology, gene regulation, toxicology, and ecological and evolutionary genetics of teleosts and other vertebrates. These explorations have reached a critical juncture at which advancement is hindered by the lack of genomic resources for these species. We suggest that a more complete genomics toolbox for F. heteroclitus and related species will permit researchers to exploit the power of this model organism to rapidly advance our understanding of fundamental biological and pathological mechanisms among vertebrates, as well as ecological strategies and evolutionary processes common to all living organisms.This material is based on work supported by grants from the National Science Foundation DBI-0420504 (LJB), OCE 0308777 (DLC, RNW, BBR), BES-0553523 (AW), IBN 0236494 (BBR), IOB-0519579 (DHE), IOB-0543860 (DWT), FSML-0533189 (SC); National Institute of Health NIEHS P42-ES007381(GVC, MEH), P42-ES10356 (RTD), ES011588 (MFO); and NCRR P20 RR-016463 (DWT); Natural Sciences and Engineering Research Council of Canada Discovery (DLM, TDS, WSM) and Collaborative Research and Development Programs (DLM); NOAA/National Sea Grant NA86RG0052 (LJB), NA16RG2273 (SIK, MEH,GVC, JJS); Environmental Protection Agency U91620701 (WSB), R82902201(SC) and EPA’s Office of Research and Development (DEN)

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations